The goal of this program is the development of a computer program (MOS/ES: modular optimization software/expert system) for the facilitation of HPLC method development. Phase I achieved the following objectives: (1) prototype expert system software that allows the development of an isocratic HPLC method, (2) a new computer-simulation module that can be used for the isocratic optimization of any separation variable (e.g., pH, ternary-solvent compositions, etc.), (3) an initial version of peak tracking software and (4) computer simulation software for the separation of large biomolecules. Phase II proposes to accomplish several tasks: (1) completion of the expert system begun in Phase I, (2) development of software based on a new approach to HPLC method development (restricted multi-parameter optimization), (3) automation of the selection of certain experimental conditions, (4) development of an interface that allows the MOS/ES program to control the HPLC hardware and (5) extension of the present approach (MOS/ES) to include preparative separations.